With the elucidation of myriad anabolic and catabolic enzyme-catalyzed cellular pathways crisscrossing each other, an obvious question arose: how could these networks operate with maximal catalytic efficiency and minimal interference? A logical answer was the postulate of metabolic channeling, which in its simplest embodiment assumes that the product generated by one enzyme passes directly to a second without diffusion into the surrounding medium. This tight coupling of activities might increase a pathway’s metabolic flux and/or serve to sequester unstable/toxic/reactive intermediates as well as prevent their access to other networks. Here, we present evidence for this concept, commencing with enzymes that feature a physical molecular tunnel, to multi-enzyme complexes that retain pathway substrates through electrostatics or enclosures, and finally to metabolons that feature collections of enzymes assembled into clusters with variable stoichiometric composition. Lastly, we discuss the advantages of reversibly assembled metabolons in the context of the purinosome, the purine biosynthesis metabolon.

随着无数合成代谢和分解代谢酶催化的细胞通路相互交叉的阐明，一个明显的问题出现了：这些网络如何以最大的催化效率和最小的干扰运行？一个合乎逻辑的答案是代谢通道的假设，在最简单的实施例中，假设一种酶产生的产物直接传递到第二种酶而不扩散到周围介质中。这种活动的紧密耦合可能会增加途径的代谢通量和/或用于隔离不稳定/有毒/反应性中间体以及阻止它们进入其他网络。在这里，我们提出了这一概念的证据，从具有物理分子隧道的酶开始，到通过静电或外壳保留途径底物的多酶复合物，最后到以具有可变化学计量组成的酶集合组装成簇的代谢物。最后，我们讨论了嘌呤体（嘌呤生物合成代谢物）背景下可逆组装代谢物的优点。